2019 – Page 2 – American ME and CFS Society

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation

Abstract:

Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning.

Methods: Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n=38) and patients with chronic pain (n=190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n=29), primary care patients (n=163), individuals from the general population (n=155) and healthy subjects (n=48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population.

Results: LPS-injected individuals (M=16.3), patients with ME/CFS (M=16.1), chronic pain (M=16.1) and primary care patients (M=10.7) reported significantly higher SicknessQ scores than individuals from the general population (M=5.4) and healthy subjects (M=3.6) all p’s<0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p’s<0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p’s<0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population.

Conclusions: Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients.

Source: Martin A.Jonsjö, JennyÅström, Michael P.Jones, Bianka Karshikoff, Karin Lodin, Linda Holmström, Lars Agréus, Rikard K.Wicksell, John Axelsson, Mats Lekander, Gunnar L.Olsson, Mike Kemani, Anna Andreasson. Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation. Brain, Behavior, & Immunity – Health. Available online 17 December 2019, 100028. https://www.sciencedirect.com/science/article/pii/S2666354619300298 (Full study)

The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients

[Editor’s Note: The dropout rate for this study was 50%. After false discovery rate (FDR) correction, none the results achieved statistical significance.]

Abstract:

BACKGROUND: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined.

METHODS: Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment.

RESULTS: Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p = 0.045, r = 0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p = 0.02, omega = 0.03, p = 0.007, r = 0.34 and p = 0.004, r = 0.35, respectively. Non-significant changes were noted in other cognitive tests.

CONCLUSIONS: A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.

Source: Zalewski P1, Kujawski S1, Tudorowska M2, Morten K3, Tafil-Klawe M4, Klawe JJ1, Strong J3, Estévez-López F5, Murovska M6, Newton JL7, The European Network On Me/Cfs Euromene. The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients. Brain Sci. 2019 Dec 19;10(1). pii: E4. doi: 10.3390/brainsci10010004. https://www.mdpi.com/2076-3425/10/1/4 (Full study)

Paediatric patients with myalgic encephalomyelitis/chronic fatigue syndrome value understanding and help to move on with their lives

Abstract:

AIM: The aim of this study was to document qualitative questionnaire feedback regarding management from a cohort observational study of young people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

METHODS: Between 1991 and 2009, 784 paediatric patients, age 6-18 years, were diagnosed with ME/CFS following referral to a specialised clinic at the Royal Children’s Hospital, Melbourne. Over a 14-year period, feedback was requested on up to seven occasions. Management included the following: symptom management and a self-management lifestyle plan that included social, educational, physical and a pleasurable activity outside of home. They adjusted it by severity of illness, stage of education, family circumstances and life interests.

RESULTS: Questionnaires were returned from 626 (80%) with 44% providing feedback more than once. They reported that their management plan allowed them to regain control over their lives. They cited early diagnosis, empathetic, informed physicians, self-management strategies and educational liaison as helping them to function and remain socially engaged. Ongoing support, particularly assistance to navigate the education system, was essential for general well-being and ability to cope.

CONCLUSION: Young people valued regaining the control over their lives that was lost through illness, support to maintain social contacts and assistance to achieve educational and/or life goals.

Source: Rowe K. Paediatric patients with myalgic encephalomyelitis/chronic fatigue syndrome value understanding and help to move on with their lives. Acta Paediatr. 2019 Dec 18. doi: 10.1111/apa.15054. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31854020

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease with no known cause or mechanism. There is an increasing appreciation for the role of immune and metabolic dysfunction in the disease. ME/CFS has historically presented in outbreaks, often has a flu-like onset, and results in inflammatory symptoms. Patients suffer from severe fatigue and post-exertional malaise. There is little known about the metabolism of specific immune cells in ME/CFS patients. To investigate immune metabolism in ME/CFS, we isolated CD4+ and CD8+ T cells from 53 ME/CFS patients and 45 healthy controls. We analyzed glycolysis and mitochondrial respiration in resting and activated T cells, along with markers related to cellular metabolism, and plasma cytokines.

We found that ME/CFS CD8+ T cells have reduced mitochondrial membrane potential compared to healthy controls. Both CD4+ and CD8+ T cells from ME/CFS patients had reduced glycolysis at rest, while CD8+ T cells also had reduced glycolysis following activation. ME/CFS patients had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from healthy control subjects.

Our data indicate that patients have impaired T cell metabolism consistent with ongoing immune alterations in ME/CFS that may illuminate the mechanism behind this disease.

Source: Mandarano AH, Maya J, Giloteaux L, Peterson DL, Maynard M, Gottschalk CG, Hanson MR. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. 2019 Dec 12. pii: 132185. doi: 10.1172/JCI132185. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31830003

Changes in circulating microRNA after recumbent isometric yoga practice by patients with myalgic encephalomyelitis/chronic fatigue syndrome: an explorative pilot study

Abstract:

BACKGROUND: Yoga is a representative mind-body therapy. Our previous studies have demonstrated that isometric yoga (i.e. yoga programs that we developed so individuals can practice yoga poses with a self-adjustable isometric load) reduces the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the underlying mechanisms remain unclear. Several studies have suggested that the micro-ribonucleic acid (miRNA) expression of ME/CFS patients is different from that of healthy subjects. However, it has not to date been determined if the practice of isometric yoga can affect miRNA expression. Therefore, we sought to investigate if isometric yoga is associated with changes in the expression levels of serum miRNA of patients with ME/CFS.

METHODS: The study included nine patients with ME/CFS who failed to show satisfactory improvement after at least 6 months of treatment administered at our hospital. Patients practiced recumbent isometric yoga for 3 months; they met with a yoga instructor every 2 to 4 weeks and participated in daily in-home sessions. The effect of recumbent isometric yoga on fatigue was assessed by comparing pre- and post-intervention scores on the Japanese version of the 11-item Chalder fatigue scale (CFQ 11). Patient blood samples were drawn pre- and post-intervention, just prior to practicing recumbent isometric yoga with an instructor. The serum was used for miRNA array analysis with known human miRNAs.

RESULTS: The average CFQ 11 score decreased significantly (from 25.3 ± 5.5 to 17.0 ± 5.8, p < 0.0001) after practicing recumbent isometric yoga for 3 months. The miRNA microarray analysis revealed that four miRNAs were significantly upregulated, and 42 were downregulated after the intervention period.

CONCLUSIONS: This explorative pilot study is the first to demonstrate changes in the serum levels of several miRNAs after regular practice of recumbent isometric yoga. These miRNAs might represent biomarkers for the fatigue-relieving effects of isometric yoga of patients with ME/CFS.

TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN CTR) 000023472. Registered Aug 4, 2016.

Source: Takakura S, Oka T, Sudo N. Changes in circulating microRNA after recumbent isometric yoga practice by patients with myalgic encephalomyelitis/chronic fatigue syndrome: an explorative pilot study. Biopsychosoc Med. 2019 Dec 2;13:29. doi: 10.1186/s13030-019-0171-2. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/31827600

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome

Abstract:

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate.

Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment.

We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.

Source: Ghali A, Lacout C, Ghali M, Gury A, Beucher AB, Lozac’h P, Lavigne C, Urbanski G. Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. Sci Rep. 2019 Dec 11;9(1):18817. doi: 10.1038/s41598-019-55473-4. ncbi.nlm.nih.gov/pubmed/31827223

Conceptualising illness and disease: reflections on Sharpe and Greco (2019)

Abstract:

In a recent paper, Sharpe and Greco suggest that chronic fatigue syndrome/myalgic encephalomyelitis (MECFS) can be viewed as an instance of “illness without disease”, and consequently, treatment should be directed towards altering the patient’s experience of, and response to, their symptoms. We discuss two broad issues that arise from Sharpe and Greco’s article, one relating to the assumptions they make about MECFS and its treatment specifically, and the other relating to their conceptualisation of the illness/disease dichotomy.

We argue that the term “illness without disease”, in the sense that Sharpe and Greco use it, is problematic because it can lead to unwarranted causal assumptions. Following these critical comments, we present a new framework for conceptualising the relationship between explanatory disease models and the experience of illness.

Source: Wilshire C, Ward T. Conceptualising illness and disease: reflections on Sharpe and Greco (2019). Med Humanit. 2019 Dec 11. pii: medhum-2019-011756. doi: 10.1136/medhum-2019-011756. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31826926 (Abstract) https://sci-hub.se/10.1136/medhum-2019-011756 (Full article)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections

Abstract:

Autoimmunity and chronic viral infections are recurrent clinical observations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex disease with an unknown cause. Given these observations, the regulatory CD4+ T cells (Tregs) show promise to be good candidates for the underlying pathology due to their capacity to suppress the immune responses against both self and microbial antigens. Here, we discussed the overlooked role of these cells in the chronicity of Human Herpes Virus 6 (HHV6), Herpes Simplex 1 (HSV1), and Epstein-Barr virus (EBV), as often reported as triggers of ME/CFS.

Using simulations of the cross-regulation model for the dynamics of Tregs, we illustrated that mild infections might lead to a chronically activated immune responses under control of Tregs if the responding clone has a high autoimmune potential. Such infections promote persistent inflammation and possibly fatigue. We then hypothesized that ME/CFS is a condition characterized by a predominance of this type of infections under control of Tregs. In contrast, healthy individuals are hypothesized to trigger immune responses of a virus-specific clone with a low autoimmune potential.

According to this hypothesis, simple model simulations of the CD4+ T-cell repertoire could reproduce the increased density and percentages of Tregs observed in patients suffering from the disease, when compared to healthy controls. A deeper analysis of Tregs in the pathogenesis of ME/CFS will help to assess the validity of this hypothesis.

Source: Sepúlveda N, Carneiro J, Lacerda E, Nacul L. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections. Front Immunol. 2019 Nov 21;10:2684. doi: 10.3389/fimmu.2019.02684. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883905/ (Full article)

Study finds differences in energy use by immune cells in ME/CFS

Press Release: New findings published in the Journal of Clinical Investigation suggest that specific immune T cells from people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) show disruptions in the way they produce energy. The research was supported by the National Institutes of Health.

“This research gives us additional evidence for the role of the immune system in ME/CFS and may provide important clues to help us understand the mechanisms underlying this devastating disease,” said Vicky Whittemore, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which partially funded the study.

ME/CFS is a severe, chronic, and debilitating disease that can cause a range of symptoms including pain, severe exhaustion, cognitive impairment, and post-exertional malaise, the worsening of symptoms after physical or mental activity. Estimates suggest that between 836,000 and 2.5 million people in the United States may be affected by ME/CFS. It is unknown what causes the disease and there are no treatments.

Research by Alexandra Mandarano and collaborators in the laboratory of Maureen Hanson, Ph.D., professor of molecular biology and genetics at Cornell University in Ithaca, New York, examined biochemical reactions involved in energy production, or metabolism, in two specific types of immune cells obtained from 45 healthy controls and 53 people with ME/CFS. Investigators focused on CD4 T cells, which alert other immune cells about invading pathogens, and CD8 T cells, which attack infected cells. Dr. Hanson’s team used state-of-the-art methods to look at energy production by the mitochondria within T cells, when the cells were in a resting state and after they had been activated. Mitochondria are biological powerhouses and create most of the energy that drives cells.

Dr. Hanson and her colleagues did not see significant differences in mitochondrial respiration, the cell’s primary energy-producing method, between healthy and ME/CFS cells at rest or after activation. However, results suggest that glycolysis, a less efficient method of energy production, may be disrupted in ME/CFS. Compared to healthy cells, CD4 and CD8 cells from people with ME/CFS had decreased levels of glycolysis at rest. In addition, ME/CFS CD8 cells had lower levels of glycolysis after activation.

“Our work demonstrates the importance of looking at particular types of immune cells that have different jobs to do, rather than looking at them all mixed together, which can hide problems specific to particular cells,” said Dr. Hanson. “Additional studies focusing on specific cell types will be important to unravel what’s gone wrong with immune defenses in ME/CFS.”

Dr. Hanson’s group also looked at mitochondrial size and membrane potential, which can indicate the health of T cell mitochondria. CD4 cells from healthy controls and people with ME/CFS showed no significant differences in mitochondrial size nor function. CD8 cells from people with ME/CFS showed decreased membrane potential compared to healthy cells during both resting and activated states.

Dr. Hanson’s team examined associations between cytokines, chemical messengers that send instructions from one cell to another, and T cell metabolism. The findings revealed different, and often opposite, patterns between healthy and ME/CFS cells, suggesting changes in the immune system. In addition, the presence of cytokines that cause inflammation unexpectedly correlated with decreased metabolism in T cells.

This study was supported in part by the NIH’s ME/CFS Collaborative Research Network, a consortium supported by multiple institutes and centers at NIH, consisting of three collaborative research centers and a data management coordinating center. The research network was established in 2017 to help advance research on ME/CFS.

“In addition to providing valuable insights into the immunology of ME/CFS, we hope that the results coming out of the collaborative research network will inspire more researchers, particularly those in the early stages of their careers, to work on this disease,” said Joseph Breen, Ph.D., section chief, Immunoregulation Section, Basic Immunology Branch, National Institute of Allergy and Infectious Diseases (NIAID), which partially funded the study.

Future research studies will examine metabolism in other subsets of immune cells. In addition, researchers will investigate ways in which changes in metabolism affect the activity of T cells.

This study was supported by NINDS grant U54NS105541, NIAID grant R21AI117595, Simmaron Research, and an anonymous private donor.

NINDS (https://www.ninds.nih.gov/) is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Reference: Mandarano et al. “Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations,” Journal of Clinical Investigation. December 12, 2019

Can you get to Worcester, Mass., to donate blood for researchers?

From Mass ME Association:

Can you get to Worcester, Mass., to donate blood for researchers?

MassME is excited to be working with Liisa Selin, PhD, and Anna Gil, PhD, of the University of Massachusetts Medical School, in Worcester, Massachusetts. Even more exciting, these trailblazing researchers were just awarded a Ramsey grant by the Solve ME/CFS Initiative. More details: https://solvecfs.org/liisa-selin-and-anna-gil/

Liisa and Anna recently said, “We are personally aware of the devastation that ME/CFS causes and the challenge of surviving each day with this disease. We are therefore very excited by our recent findings of a unique subset of T cells that may play a role in ME/CFS immunopathogenesis and its potential to be a biomarker.”

Want to show these ME/CFS researchers a little love? Can you make the trip to Worcester, MA, 1 hour west of Boston to donate blood? They are looking for men and women aged 18 years or older with ME/CFS. Healthy men and women aged 18 years or older are also welcome.

Blood donors get $20. The researchers would need at least 30 mL of your blood — and up to 60 mL, if you are willing and able. They would like to get the first set of blood samples in December and before January 21st. The first scheduled date and time is this coming Monday, December 16, from 2 pm to 4 pm. Please contact our coordinator Jeanne Perrin at <jeanne2911@outlook.com> or 781-392-4708 as soon as possible if you can join us on Monday or to arrange another time. Jeanne will give you location and parking information.

Please feel free to forward this notice to other people with ME/CFS who might be interested.